Potapova Tamara, Gorbsky Gary J
Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
Cell Cycle and Cancer Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Biology (Basel). 2017 Feb 8;6(1):12. doi: 10.3390/biology6010012.
Mistakes during cell division frequently generate changes in chromosome content, producing aneuploid or polyploid progeny cells. Polyploid cells may then undergo abnormal division to generate aneuploid cells. Chromosome segregation errors may also involve fragments of whole chromosomes. A major consequence of segregation defects is change in the relative dosage of products from genes located on the missegregated chromosomes. Abnormal expression of transcriptional regulators can also impact genes on the properly segregated chromosomes. The consequences of these perturbations in gene expression depend on the specific chromosomes affected and on the interplay of the aneuploid phenotype with the environment. Most often, these novel chromosome distributions are detrimental to the health and survival of the organism. However, in a changed environment, alterations in gene copy number may generate a more highly adapted phenotype. Chromosome segregation errors also have important implications in human health. They may promote drug resistance in pathogenic microorganisms. In cancer cells, they are a source for genetic and phenotypic variability that may select for populations with increased malignance and resistance to therapy. Lastly, chromosome segregation errors during gamete formation in meiosis are a primary cause of human birth defects and infertility. This review describes the consequences of mitotic and meiotic errors focusing on novel concepts and human health.
细胞分裂过程中的错误常常会导致染色体含量发生变化，产生非整倍体或多倍体子代细胞。多倍体细胞随后可能会经历异常分裂以产生非整倍体细胞。染色体分离错误也可能涉及整条染色体的片段。分离缺陷的一个主要后果是位于错误分离染色体上的基因产物相对剂量的改变。转录调节因子的异常表达也会影响正确分离染色体上的基因。这些基因表达扰动的后果取决于受影响的特定染色体以及非整倍体表型与环境的相互作用。大多数情况下，这些新的染色体分布对生物体的健康和生存有害。然而，在变化的环境中，基因拷贝数的改变可能会产生适应性更强的表型。染色体分离错误在人类健康方面也具有重要意义。它们可能会促进致病微生物产生耐药性。在癌细胞中，它们是遗传和表型变异的一个来源，可能会选择出恶性程度增加和对治疗耐药的细胞群体。最后，减数分裂过程中配子形成时的染色体分离错误是人类出生缺陷和不孕不育的主要原因。本综述描述了有丝分裂和减数分裂错误的后果，重点关注新的概念和人类健康。
